Processing of biological materials often involves the automated transfer of sample materials onto reaction points for testing and analysis. Microarrays have been used to execute tests on large batches of genetic samples to generate phenotype associations and improve interpretation of the large data sets that result from such tests. Samples are usually prepared in a tray called a microtiter plate (MTP), which contains an array of wells that each hold a sample of biological material. A variety of liquid reagent materials are combined in the wells and are subjected to various processes, such as, for example, the polymerase chain reaction (PCR) process, which is a method of amplifying DNA for analysis.
According to the PCR process, a small amount of DNA is replicated by mixing DNA samples with various agents and subjecting the samples to a thermal cycling process in which the samples are subjected to alternating series of heating and cooling cycles. In a typical thermal cycling operation, an MTP with samples is placed in a thermal cycler booth, where the MTP plate is heated and cooled, as desired, thereby affecting the contents of the MTP wells. One way of heating and cooling the plate is to place the plate on top of a metal plate that conforms to the underside of the MTP. The metal plate is heated and cooled, which also causes the MTP to heat and cool.
Prior to the thermal cycling process, the sample preparation for PCR typically begins with empty MTPs being delivered to a plate processing station. The various reagents and biological materials are then added to the wells of the MTP, using robotic systems that pick up the MTPs from a plate processing station, add reagents to the biological material samples, and then move the MTP to a next station for further processing. Alternately, a human operator can manually add and mix the reagents and the biological materials. Thus, the wells of an MTP often contain sample materials that are themselves the result of several operations, usually involving the mixing of solutions and other processing in each of the wells, to prepare the sample materials for PCR. The MTP may be moved to several different stations during such operations, such as stations where the MTPs are rinsed and where samples are moved from the wells of one MTP to the wells of another MTP.
After the PCR process is complete for a given set of samples, the resultant sample materials can be subject to one or more additional processes, which often necessitates washing and rinsing of the equipment that was used for the previous processes. The final samples are often placed in an array of spots on a substrate and then are subject to one or more analyses, such as Matrix Assisted Laser Desorption/Ionization mass spectrometry (MALDI-MS), which is known to those of skill in the art. According to the MALDI-MS process, the samples contained in spots on a target plate are dispersed in a matrix material that strongly absorbs light of a certain wavelength. In a vacuum chamber, short pulses of laser light are then focused on to the samples to cause the samples and matrix to volatilize and form ions. The ions formed are accelerated by a high voltage supply and then allowed to drift down a flight tube. Scientists can glean information about the molecular weight of sample components, based on the amount of time it takes for the ions to arrive at the end of the flight tube.
There are a variety of costs that are associated with the aforementioned processes. One such cost is in terms of the relatively large amount of time that it takes to perform the processes, which decreases throughput of sample analysis. The time required to perform the processes is due to a variety of factors. For example, in the thermal cycling process, the cooling and heating of the MTPs can consume a large amount of time, such as on the order of several hours. It also takes time to move the MTPs between the various stations, such as from the mixing stations where the samples are prepared, to the thermal cycling stations where thermal cycling is performed. Another time drain occurs after PCR and other reactions that follow, when the samples are removed from the MTPs and deposited on a substrate for MALDI-MS.
Another cost is in terms of the amount of space required to perform the processes. Currently, several stations are required to be used during the process, each of which consumes space that could be used for other purposes. The various stations also require some mechanism for transferring the samples between the stations, such as in the form of a robotic system or human operators that increase the monetary costs of the processes. Yet another cost relates to the volume of supplies that are needed to perform the processes. For example, the reagents that are used during PCR are quite expensive.
In view of the foregoing, there is a need for improved apparatus and method of processing biological samples that alleviates the various costs associated with such analysis.